1. Field of the Invention
The present invention relates to a kit for diagnosis of dementia comprising the novel Aβ22(pE)-42 peptide binding specifically to amyloid-beta antibody in blood as an active ingredient
2. Description of the Related Art
Population aging in Korea and in most of other countries increases interest in senile diseases and accordingly studies have been actively undergoing about senile diseases. Alzheimer's disease is a kind of degenerative diseases and one of the most representative dementia related diseases, which puts heavy mental and physical burden on the shoulder of not only patient himself but also his family. Alzheimer's disease is found in 10% of people at the age of 65˜74, 19% of people at the age of 75˜84, and 47% of people at the age of 85 and up. Incidence rate of the disease rises every year, which becomes a serious social problem.
None of the prevention method for Alzheimer's disease or the method for early diagnosis has been known so far. Diagnosis of the disease has depended on doctor's clinical opinion and neuropsychological test, indicating only after the disease progresses far, diagnosis can be made, which makes the treatment difficult. Any effective therapeutic agent has not been developed, yet. Compositions for alleviating symptoms are just used.
The most acceptable theory to understand the mechanism of Alzheimer's disease now is “amyloid hypothesis”. That is, amyloid-beta existed in patients or plaque generated by amyloid-beta accumulation induces continuous apoptosis of neurons, resulting in the suppression of neuronal transmission and damages in recognition, leading to the outbreak of Alzheimer's disease. Senile plaque and neurofibrillary tangles are observed in the brains of expired patients due to Alzheimer's disease, which are major pathological characteristics of Alzheimer's disease. Particularly, senile plaque is formed by the accumulation of protein and dead cells in outer cell whose major component is a peptide called amyloid-beta (Aβ) (Hardy, J. et al, Nat Neurosci. 1:355-358, 1998). Gradual damage in recognition, which is the major characteristics of Alzheimer's disease, is believed to be caused by abnormal accumulation of amyloid-beta that is produced by proteolysis of amyloid precursor protein (referred as “APP” hereinafter). The precursor APP is decomposed by β-secretase (BSCE) and γ-secretase to generate amyloid-beta (Craven, R., Nat Rev. Neurosci. 2: 533, 2001; David, H. S. et al., Nat Rev. Neurosci. 2: 595-598, 2001; Yankner, B. A., Neuron 16: 921-932, 1996; Selkoe, D. J., Nature 399: A23-A31, 1999). Development of diagnosis indexes for Alzheimer's disease from blood is actively undergoing. Recently, amyloid protein (amyloid-beta, Aβ42, and Aβ40) known as a key player in Alzheimer's disease development is used as standard for the diagnosis of Alzheimer's disease.
In animal models having Alzheimer's disease, the levels of Aβ42 and Aβ40 in serum and cerebrospinal fluid are increased in proportion to aging. Once cognitive impairment starts, the levels of those proteins are decreased. Thus, taking the amyloid protein level in serum as a standard index for the diagnosis of Alzheimer's disease is under controversy. It has been known that amyloid antibody is observed in the brain, blood, and cerebrospinal fluid of both normal healthy people and Alzheimer's disease patients, but the amount or characteristics of amyloid antibody have not been explained, yet.
The method for early diagnosis of Alzheimer's disease and the prevention method thereof have recently been focused on measuring amyloid-beta protein in body by using amyloid-beta antibody. In this method, it is very important to identify amyloid-beta antigen having a specific arrangement binding specifically to the antibody growing specifically in the blood of Alzheimer's disease patients, unlike in normal people.
Therefore, the present inventors screened peptides having specific patterns that bind specifically to amyloid-beta antibody and then confirmed that Aβ22(pE)-42 peptide had comparatively high reactivity against amyloid-beta in serum of Alzheimer's disease patients, compared with in normal people. Accordingly, the present inventors completed this invention by confirming that the said Aβ22(pE)-42 peptide can be used as an active ingredient for the diagnostic kit of dementia and for the diagnosis of dementia whose early diagnosis is very difficult so far.